PROGRAM

March 2013

In the fi rst seven weeks of this year more than 200,000 people in Brazil were reported to have dengue, up 190% (from 70,000) for the same period last year. Singapore has seen an almost four-fold increase in the number of reported cases, while Taiwan has recorded ‘an all time high’ in the number of imported cases.

It is particularly timely that in the coming weeks we will begin the fi rst trials of our dengue control method in south east Asia, deploying mosquitoes with the strongest dengue blocking Wolbachia strain.

As fi eld trials move to other countries, our aim is to maintain the high standard of community engagement demonstrated in Australia and Vietnam and ensure ongoing support from the public, governments and their regulatory agencies.

I invite you to follow our progress through our website(www.eliminatedengue.com) and encourage any questions you may have about our work by emailing us (contact@eliminatedengue.com)

Professor Scott O’NeillProgram Leader

In April the Eliminate Dengue project in Vietnam will release the fi rst Wolbachia Aedes aegypti mosquitoes on Tri Nguyen Island (TNI) 1 kilometre from the port of Nha Trang in Khanh Hoa province, in central Vietnam.

In preparation for this trial, and the fi rst for the Wolbachia dengue control method outside of Australia, project members have been concentrating their eff orts in the rearing of Wolbachia mosquitoes at the National Institute of Hygiene and Epidemiology in Hanoi, and the Institute Pasteur Nha Trang, and reducing wild mosquito populations on Tri Nguyen Island.

The trial will involve the deployment of mosquitoes, with the strongest dengue blocking Wolbachia strain, once a week for 3 months. To facilitate this, locally recruited collaborators will visit homes each week to place a small cup holding Wolbachia Aedes aegypti pupae or immatures, (the fi nal stage before a mosquito becomes an adult) in a small basket that has been placed at each home.

The adult mosquitoes will emerge from the cup over the next day or two to disperse and breed with local wild mosquitoes. We will then measure the levels of Wolbachia in the Aedes aegypti population on the island through a network of monitoring traps and report the progress.

In Yogyakarta while community engagement activities continue in potential trial sites across the city, the project has offi cially opened a dedicated Wolbachia and dengue diagnostic facility at the University of Gadjah Mada (UGM) made possible through support from project funders, Yayasan Tahija.

The laboratory, under the leadership of Dr Eggi Arguni (pictured above far left), will establish protocols for screening and quality assurance testing for the Wolbachia trial in Indonesia.

On 5th March 2013, Mr Wahyuhadi, Chair of Yayasan Tahija marked the offi cial opening of the diagnostic laboratory with Professor Teguh Aryandono, Dean of the Faculty of Medicine, UGM. The lab has been dedicated to and named after ‘Yayasan Tahija’.

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Ready for a first trial in VietnamFollow our research

Opening of lab at UGM

VIETNAM

www.eliminatedengue.com

INDONESIA

www.eliminatedengue.com

Eliminate Dengue project partners in China have formally submitted an application for regulatory approval to the Chinese Ministry of Agriculture to implement the Wolbachia dengue control method there. If successful, China will be the fi rst country to gain approval to trial the method on Aedes albopictus, the Asian tiger mosquito.

In southern China local dengue transmission only occurs via Aedes albopictus. This is diff erent to most tropical regions of the world where Aedes aegypti is the main dengue vector. Aedes albopictus naturally carries two Wolbachia strains. Dr Zhiyong Xi, Lead Scientist, Eliminate Dengue China and his team have developed a triple-infected Aedes albopictus mosquito strain that may eff ectively control dengue in southern China. With regulatory approval and community support the project aims to undertake a fi eld trial to see whether this Wolbachia strain can establish within wild mosquito populations in Guangzhou, Guangdong province.

The Eliminate Dengue project in Brazil, Eliminar a Dengue: Desafi o Brasil has identifi ed four areas across the cities of Rio de Janeiro and Niteroi as potential fi eld sites to trial the Wolbachia dengue control method in Brazil.

Researchers from the Oswaldo Cruz Foundation (Fiocruz) and health agents from the respective municipal governments are monitoring mosquito populations in these sites and meeting with community members to introduce and explain the Eliminar a Dengue project (pictured above).

Urca, Tubiacanga and Vila Valqueire are sites within the municipality of Rio de Janeiro. The fourth site is Jurujuba, across Guanabara Bay in the municipality of Niteroi. All sites are relatively isolated and off er diverse geographic and demographic challenges for the project. he project team is currently seeking regulatory approval and community support for future fi eld trials in these sites. Follow the progress at www.eliminatedengue.com/project/brazil

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China seeks regulatory approval

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The Eliminate Dengue research program is a not-for-profi t,

international collaboration led from Monash University, Melbourne.

Our research is funded by:

• The Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative

of the Bill & Melinda Gates Foundation• Yayasan Tahija, Indonesia

• The Australian and Queensland Governments

• The Brazilian Government

Program Newsletter March 2013

On 10th January 2013 we began a third trial in Cairns, Australia.

This trial involves the release of mosquitoes with the same Wolbachia strain as the 2011 trial. The current trial will test how well Wolbachia may establish in more populated and less contained areas of the inner city suburbs of Cairns, rather than in the contained, isolated areas of the 2011 trial*.

After eight weeks of releases (to 6 March) we are seeing medium to high numbers of Wolbachia carrying mosquitoes in the three trial sites (see www.eliminatedengue.com/progress). These results are encouraging but we will not know for some months if Wolbachia is being maintained in the mosquito population.

*Over 24 months after the last controlled release of Wolbachia mosquitoes in Yorkeys Knob and Gordonvale close to 100% of Aedes aegypti mosquitoes still have Wolbachia which we believe will mean a reduced risk of local dengue transmission, if the virus is brought into these areas.

A short video about our research is now available in English, Bahasa Indonesia, Vietnamese and Portuguese.

Visit www.eliminatedengue.com

Third Cairns trial

Brazil sites selected BRAZIL

CHINA

Insect-transmitted diseases are present in more than 100 countries worldwide, predominantly in developing countries in the tropics (FIG. 1a). Although progress is currently being made in combatting some of these dis-eases, including malaria, Chagas disease and filariasis, case burdens are still high, and for some diseases (for example, dengue), the problem is worsening globally. One-sixth of the world’s infection-associated DALY (disability-adjusted life year) estimate is attributed to vector-borne disease, and more than 90% of this fraction is due to mosquito-transmitted agents; in fact, malaria parasites contribute more to the burden than any other pathogen1 (FIG. 1b). Recent WHO estimates predict that there are 50–100 million cases of dengue per year — second only in the vector-borne diseases to malaria (for which there are 216 million cases annually). But meas-ures such as DALY, incidence or annual mortality rate for a disease greatly underestimate the importance of the disease to communities. When the social and economic impacts of diseases like dengue are also considered, then the enormity of their effect on communities can be fully appreciated2,3.

For many years, much of the medical research com-munity has been focused on the development of vaccines or drugs for mosquito-borne diseases. As yet, there is no effective vaccine for malaria, although Phase III trials of the most advanced vaccine, RTS S/AS01 (which is being developed by GlaxoSmithKline, PATH and the Bill and Melinda Gates Foundation), are showing some promise, with up to a 50% reduction in disease rates in African children4. The development of vaccines for malaria has been slow owing to the complexity of the different life

stages of the parasite and our poor understanding of the human immune response correlates. Ultimately, multiple vaccines might be required to target differ-ent life stages as well as different parasite species5. The current antimalarial drugs of choice include a range of artemisinin-based combination therapies6. These drugs function well to limit mortality and are fairly low risk for the development of resistance7. However, there is a need for drugs that can kill all stages of the parasite in a single dose if this approach is to be effective in the push for malaria eradication8. By contrast, there are few, if any, drugs available for treatment of the major arbovirus diseases9. Instead, greater progress has been made with the preventative, vaccine-based approach, from the yellow fever vaccine developed in the 1930s10 through to the more recently developed vaccines for Japanese encephalitis (reviewed in REF. 11). Several vac-cines are in development for dengue, the most advanced of which has just recently completed Phase IIb field trials in Thailand, with mixed results12. Vaccine design for dengue has been far more challenging than for other arbovirus diseases owing to the existence of multiple serotypes, the complexity of the human immune response to dengue virus and the propensity for sequential infections to result in more severe forms of the disease13. Great strides have also been made in targeting lymphatic filariasis with mass drug adminis-tration of anthelmintics, chiefly ivermectin. However, effective, long-term treatment of populations with anthelmintics has its challenges with respect to sus-tained delivery and coverage as well as potential resist-ance in the nematode14. For all these diseases, some of

1School of Biological Sciences, Monash University, Clayton, Victoria 3800, Australia.2Institute of Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.Correspondence to S.L.O.  e-mail:scott.oneill@monash.edudoi:10.1038/nrmicro2968

DALY(Disability-adjusted life year). The number of years lost owing to morbidity or mortality of a disease. This measure is preferable to simple mortality measures, as it better captures the disease burden for debilitating but often self-limiting diseases like dengue and malaria.

Beyond insecticides: new thinking on an ancient problemElizabeth A. McGraw1 and Scott L. O’Neill1,2

Abstract | Vector-borne disease is one of the greatest contributors to human mortality and morbidity throughout the tropics. Mosquito-transmitted diseases such as malaria, dengue, yellow fever and filariasis are the main contributors to this burden. Although insecticides

substantial progress has been made in developing alternative vector control strategies ranging from biocontrol methods through to genetic modification of wild insect populations. Here, we review recent advances concerning these strategies and consider the potential impediments to their deployment, including the challenges of obtaining regulatory approval and community acceptance.

V E C TO R - B O R N E D I S E A S E S

REVIEWS

NATURE REVIEWS | MICROBIOLOGY VOLUME 11 | MARCH 2013 | 181

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AUSTRALIA

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